Medical endoprostheses or implants for a wide range of applications are known in a large variety from the prior art. Implants in the meaning of the present invention are to be understood as endovascular prostheses or other endoprostheses, for example stents, fastener elements for bones, for example screws, plates or nails, surgical sutures, intestinal staples, vascular clips, prostheses in the region of the hard and soft tissue, and anchor elements for electrodes, in particular of pacemakers or defibrillators.
Today, particularly frequently used as implants are stents which serve for the treatment of stenoses (vasoconstrictions). Stents have a body in the form of an open-worked tubular or hollow-cylindrically basic grid which is open at both longitudinal ends. The tubular basic grid of such an endoprosthesis is inserted into the vessel to be treated and serves for supporting the vessel. Stents are established in particular for the treatment of vascular diseases. By using stents or other implants, constricted areas in the vessels can be expanded, thereby resulting in a lumen gain. By using stents or other implants, an optimal vessel cross-section, which is primarily necessary for the success of the therapy, can be achieved; however, the permanent presence of such a foreign body initiates a cascade of microbiological processes which can result in a gradual constriction of the stent, and in the worst case in a vascular occlusion.
An approach for the solution of this problem is to produce the stent or other implants from a biodegradable material.
Biodegradation is to be understood as hydrolytic, enzymatic and other metabolic-related degradation processes in a living organism which are mainly caused by body liquids which get in contact with the biodegradable material of the implant and which result in a gradual degradation of the structures of the implant containing the biodegradable material. Through this process, the implant loses its mechanical integrity at a certain point in time. As a synonym for the term biodegradation, the term biocorrosion is frequently used. The term bioresorption comprises the subsequent resorption of the degradation products by the living organism.
Suitable materials for the body of biodegradable implants can contain, for example, polymers or metals. The body can consist of a plurality of said materials. A common feature of said materials is their biodegradability. Examples for suitable polymeric compounds are polymers from the group cellulose, collagen, albumin, casein, polysaccharides (PSAC), polyactide (PLA), poly-L-lactide (PLLA), polyglycol (PGA), poly-D,L-lactide-co-glycolide, (PDLLA-PGA), polyhydroxybutyrate (PHB), polyhydroxyvaleric acid (PHV), polyalkyle carbonate, polyorthoester, polyethylene terephthalate (PET), polymalonic acid (PML), polyanhydrides, polyphosphazenes, polyamino acids and their co-polymers, and hyalaronic acid. The polymers can be available depending on the desired properties in pure form, in derivatized form, in the form of blends, or as co-polymers.
The present invention relates to implants made of a metallic biodegradable material based on iron or iron-based alloys (hereinafter in short: iron alloy).
Already known are stents which have coatings with different functions. Such coatings serve, for example, for releasing drugs, arranging a x-ray marker, or for protection of the underlying structures.
When implementing biodegradable implants, the degradability is to be controlled according to the intended therapy or the application of the respective implant (coronary, intracranial, renal, etc.). For many therapeutic applications it is, for example, an important target corridor that the implant loses its integrity within a time period of four weeks to six months. Here, integrity, i.e., mechanical integrity, is to be understood as the property that the implant barely experiences any mechanical shortcomings with respect to the non-degradable implant. This means that the implant is mechanically stable such that, for example, the collapse pressure has dropped only insignificantly, i.e., not below 80% of the nominal value. Thus, with existing integrity, the implants still meet its main function which is to keep the vessel open. Alternatively, integrity can be defined in that the implant is mechanically stable such that it is barely subject of any geometrical changes in its loaded state in the vessel, for example, does not collapse significantly, i.e., shows under load at least 80% of the dilatation diameter or, in case of a stent, has barely any partially fractured supporting webs.
Implants with an iron alloy, in particular ferrous stents, are producible in a particularly inexpensive and simple manner. However, for example for the treatment of stenoses, these implants lose their mechanical integrity or supporting effect only after a relatively long period of time, i.e. only after a retention period in the treated organism of approximately 2 years. This means that the collapse pressure for ferrous implants decreases too slow over time for the desired applications.
In the prior art, different mechanisms for controlling degradation of implants have already been described. They are based, for example, on inorganic or organic protection layers or their combinations which resist the human corrosive environment and the corrosion processes taking place therein. Previously known solutions are characterized in that barrier layer effects are achieved which are based on a spatial and preferably defect-free separation of the corrosion medium from the metallic medium. Said effects result in that the degradation time is extended. Thus, the degradation protection is ensured through differently composed protection layers and by defined geometrical distances (diffusion barriers) between the corrosion medium and the basic magnesium material. Other solutions are based on specifically changing alloying constituents of the biodegradable material of the implant body. However, with the aforementioned solutions it is in most cases not possible to bring the dissolution initiated by the degradation process and the resulting web breakages into the desired time window. The consequence, in particular in case of implants containing an iron alloy, is a degradation that starts too late, or an excessive variability of the degradation of the implant.
Another problem in connection with coatings is the fact that stents or implants normally assume two different states, namely a compressed state with a small diameter and an expanded state with a larger diameter. In the compressed state, the implant can be inserted by means of a catheter into the vessel to be supported and can be positioned at the position to be treated. At the site of treatment, the implant is then dilated, for example by means of a balloon catheter. Due to the diameter change, the body of the implant is subjected here to a heavy mechanical load. Further mechanical loads on the implants can occur during the production of the implant or during movement of the implant in or with the vessel in which the implant is inserted. The above mentioned coatings thus have the disadvantage that a coating breaks during the deformation of the implant (e.g. formation of micro cracks) or is partially removed. Hereby, an unspecified local degradation can be caused. Moreover, the start and the speed of the degradation depend on the size and the distribution of the micro cracks generated by the deformation, which, as defects, are difficult to control. This results in a high variance of the degradation times.
From the printed publications US 2008/0086195 A1 and WO 2008/045184 A1, a medical device such as a catheter or a stent is known on which a polymer-free coating is applied by means of a plasma electrolytic deposition (PED). The plasma electrolytic coating is used for introducing additional active ingredients into the coating which contain a drug or a therapeutic agent. The plasma electrolytic coating comprises a plasma electrolytic oxidation (PEO), a micro-arc oxidation (MAO), a plasma-arc oxidation PAO), an anodic spark oxidation, and a plasma electrolytic saturation (PES). The plasma electrolytic treatment includes the use of different electrical potentials between the medical device and a counter electrode which generates an electrical discharge (a spark or arc plasma micro discharge) on the surface or near the surface of the medical device and which does not cause a significant extension of the degradation times. Thus, the method disclosed in the above mentioned printed publications does not solve the above mentioned problem.